doi:10.1507/endocrj.EJ23-0078

Original

Efficacy of testosterone replacement treatment forpatients with symptoms of late-onset hypogonadism
based on real-world patient satisfaction
Keisuke Ishikawa1), 2), Akira Tsujimura2), Miho Miyoshi2), Yuto Miyoshi2), Taiki Ogasa2),
Ippei Hiramatsu1), 2), Yuka Uesaka2), Taiji Nozaki2), Masato Shirai2), Kazuhiro Kobayashi3) and
Shigeo Horie1)
1)

Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo 113-8421, Japan
Department of Urology, Juntendo University Urayasu Hospital, Chiba 279-0021, Japan3)
D Clinic Tokyo, Tokyo 100-6210, Japan
2)

Abstract. Late-onset hypogonadism is generally treated with testosterone replacement treatment. However, the efficacy rateof treatment for patients with low testosterone is not clear because patients without low testosterone are also treated in realworld clinical settings. This study comprised 110 men with low testosterone concentration of <3.0 ng/mL who underwent
testosterone replacement treatment. Physical factors, laboratory and endocrinologic profiles, and scores of several
questionnaires were assessed. Testosterone replacement treatment was performed with intramuscular injection of 250 mg of
testosterone esters every 2–4 weeks, and efficacy was judged by patient satisfaction. After confirming efficacy, changes inseveral factors by the treatment were evaluated. Finally, the comparison between evaluation by patient satisfaction and by thatwith the questionnaires was assessed. Among the 110 patients, 77 (70.0%) were satisfied with the treatment, which was
effective in 65.7%, 71.4%, and 73.1% of patients with mental, physical, and sexual dysfunction, respectively. The
questionnaire scores including the Aging Males Symptoms rating scale were significantly improved in both the satisfaction
and non-satisfaction group. However, no significant differences in the amount of change in questionnaire scores were foundfor all questionnaire scores improved by testosterone replacement treatment between the groups. Patient satisfaction was not
associated with improvement of the Aging Males Symptoms score. Although testosterone replacement treatment was effective
for 70.0% of the hypogonadal patients, patient satisfaction did not correlate with improvement of questionnaire scores. We
concluded that not only questionnaire results but also patient satisfaction is important when evaluating efficacy in patients
undergoing testosterone replacement treatment.
Key words: Aging Males Symptoms rating scale, Effective rate, Late-onset hypogonadism, Patient satisfaction, Testosterone
replacement treatment

TESTOSTERONE plays an important role physiologi‐
cally in several organs and tissues in which androgen
receptors locate, such as skin, muscle, liver, bone andSubmitted Feb. 22, 2023; Accepted May 12, 2023 as EJ23-0078
Released online in J-STAGE as advance publication Jun. 21, 2023

Correspondence to: Akira Tsujimura, Department of Urology,
Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu,
Chiba 279-0021, Japan.
E-mail: atsujimu@juntendo.ac.jp
Abbreviations & Acronyms: AMS, Aging Males Symptoms rating
scale; BDI, Beck Depression Inventory; BMI, body mass index;
EAU, European Association of Urology; EHS, Erection Hardness
Score; FSH, follicle-stimulating hormone; IPSS, International
Prostate Symptom Score; LH, luteinizing hormone; LOH, lateonset hypogonadism; NSG, non-satisfaction group; SG, satisfac‐
tion group; SHIM, Sexual Health Inventory for Men; TRT,
testosterone replacement treatment©The Japan Endocrine Societybone marrow, brain, and sexual organs [1]. Recently, theconcept of late-onset hypogonadism (LOH), defined as“a clinical and biochemical syndrome associated withadvancing age and characterized by typical symptoms
and a deficiency in serum testosterone levels” by theEuropean Association of Urology (EAU) and others, hasgained increased attention in the current aging society
because testosterone decreases gradually as a part of
the aging process [2]. In general, characteristic symp‐
toms of LOH include mental symptoms such as de‐pression, anger, and lack of concentration; physicalsymptoms such as fatigue, a decrease in lean body mass
with associated decrease in muscle volume and strength,a decrease in bone mineral density resulting in osteo‐
porosis, increased body fat, and diabetes; and sexual
symptoms such as decreasing sexual desire and erectile

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Ishikawa et al.

dysfunction [3-7]. We have usually treated middle-aged
to elderly patients complaining of at least one of theabove-listed symptoms with testosterone replacement
treatment (TRT) when their serum concentration of
testosterone was low. However, along with the highrecognition of LOH, two major issues have been high‐lighted: one is the rate of effectiveness of TRT, and theother is evaluation of the efficacy of TRT.
Regarding the former, only two studies have reported
on the rate of treatment effectiveness for patients withsymptoms of LOH. One study showed a rate of effective‐
ness of 63.8% for the treatment in patients with symp‐
toms of LOH [8]. However, that study included patientstreated not only with TRT but also with herbal medicine.
In addition, the judgement of treatment efficacy in thatstudy was not defined clearly. The other study showedthat the rate of effectiveness for patients with symptomsof LOH, whose median serum testosterone concentration
was within normal limits (3.64 ± 1.34 ng/mL) was 70.9%[9]. However, those patients were treated with herbal
medicine and not by TRT. Until the present study, to ourknowledge, no study has reported the rate of effective‐
ness of TRT for patients with symptoms of LOH as
judged by patient satisfaction.
Regarding the latter, improvement of the Aging Males
Symptoms rating scale (AMS) score has been used clini‐cally and in several meta-analyses [10, 11]. The AMS
is actually recommended by the American Endocrine
Society [12] and is generally used in many facilities
in Japan. In addition, questionnaires such as the Beck
Depression Inventory (BDI) for mental symptoms, Sexual
Health Inventory for Men (SHIM), and Erection Hardness
Score (EHS) for sexual symptoms have been used sup‐plementarily. Although many reports showed that TRT
improved the score of each questionnaire, no reports
have examined the relationship between patient satisfac‐
tion with TRT and improvement in each of the question‐
naires [13-15].
In the present study, we thus aimed to clarify the rateof effectiveness of TRT in patients with low serum
testosterone concentration based on patient satisfaction.
We further compared the metabolic, endocrinological,
and symptomatic characteristics before and after TRT.
Finally, we investigated the relationship between patientsatisfaction and improvement of the questionnaire scores
after TRT by two comparative strategies.

Materials and Methods
This study comprised 110 men who visited our hospi‐
tal or affiliated clinic between March 2012 and March2018 and had undergone TRT. We set the critical cutoff
value of low testosterone concentration for the indicationof TRT at 3.0 ng/mL in reference to the guideline of theAmerican Urological Association and Endocrine Society[16, 17]. They suggest the presence of at least one
symptom of LOH as follows: lethargy, general fatigue,malaise, depression, insomnia, frustration, reduced
concentration, sweating, hot flashes, coldness, tinnitus,
headache, numbness, dizziness, stiff shoulder, night
sweats, sexual dysfunction, and decreased libido. All
blood samples were collected between 09:00 and 11:00
to monitor endocrinological variables before and after
TRT considering the fact that testosterone levels dependon the timing after injection. Blood testosterone levels
taper off after injection of testosterone. As most of thepatients at our institution continued injections at 4-weekintervals, we basically performed blood sampling at thesecond week after injection to evaluate the average value
over the interval period [18]. Physical and laboratory
data included age, body mass index (BMI; body weight[kg]/height2 [m2]), serum concentrations of total choles‐
terol, high-density lipoprotein cholesterol, low-density
lipoprotein cholesterol, triglyceride, uric acid, fastingblood sugar, and hemoglobin A1c. Endocrinologic data,
including luteinizing hormone (LH), follicle-stimulating
hormone (FSH), total testosterone, prolactin, dehydro‐
epiandrosterone sulfate, insulin-like growth factor 1,
insulin, and cortisol were also evaluated. LH, FSH, andtestosterone were measured by radioimmunoassay.
Prolactin, IGF-1, and cortisol were measured by electro‐
chemiluminescence immunoassay. DHEA-S and insulin
were measured by chemiluminescent enzyme immuno‐
assay. We assessed symptoms by several specific ques‐tionnaires including the IPSS for voiding symptoms, theBDI for depression, the SHIM and EHS for sexual func‐tion, and the AMS for LOH. Patients with suspected
severe endocrine and metabolic disease or mental disease
were excluded. TRT consisted of intramuscular injectionof 250 mg of testosterone esters every 2–4 weeks for 3
months according to the clinical practice manual for
LOH syndrome by the Japanese Urological Associationand the Japanese Society of Men’s Health [19]. Efficacy
was judged based on patient determination of satisfaction
or lack thereof at 3 months after TRT. Patient satisfaction
was solely assessed in an interview between the attending
physician and the patients. Patients were asked during
the treatment decision period, “Were you happy with thistreatment?” and the satisfaction level was evaluatedbased on their answer. If patient satisfaction was equiv‐
ocal, TRT was judged as being ineffective. Satisfied
patients were defined as the satisfaction group (SG), andunsatisfied patients and/or patients lost to follow-up
within 3 months were defined as the non-satisfactiongroup (NSG). Improvement based on the AMS wasassessed by a decrease in the AMS score of ≥8 points,

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Testosterone replacement treatment

which was the middle value of the change in AMS score
in all patients.
First, we calculated the rate of effectiveness of TRT.
Second, we compared the metabolic and endocrino‐
logical as well as symptomatic characteristics before andafter TRT in both the SG and NSG. Third, we compared
the change in the scores of all questionnaires between the
SG and the NSG. Fourth, we compared the ratio of
patient satisfaction between the group with successfultreatment as assessed by a change in the AMS score of≥8 points and the group with failed treatment as assessedby a change in the AMS score of ≤7 points.
This study was conducted in accordance with the
Declaration of Helsinki and Good Clinical Practiceguidelines, and written informed consent was obtained
from all patients. The procedures were approved by
the Regional Ethics Committee of Juntendo Urayasu
Hospital, Urayasu, Japan (approval no. 2018-029) andthe D Clinic Tokyo for men.

Statistical analysis
Data and scores of the questionnaires are presented
as the mean ± standard error. The paired t-test was used
to compare these factors before and after TRT in the SG
and NSG. The relation between patient satisfaction andthe change in the AMS score was assessed with theMann-Whitney U test and Chi-squared test. Statisticalsignificance was set at p < 0.05. Statistical analyses
were conducted with SPSS version 24.0 (SPSS, Chicago,
IL, USA).

Table 1

Characteristics of the 110 patients
Value

Number of cases

Range

110

Chief complaint
Mental symptom

35 (31.8%)

Physical symptom

49 (44.6%)

Sexual dysfunction
Age (y)26 (23.6%)
53.5 ± 8.7(40–86)

2

BMI (kg/m )25.1 ± 3.7(16.0–37.0)

Total cholesterol (mg/dL)

213.2 ± 53.0

(122–546)

HDL cholesterol (mg/dL)

56.8 ± 14.5

(27–102)

LDL cholesterol (mg/dL)

122.2 ± 36.7

(15–245)

Triglyceride (mg/dL)

218.0 ± 399.5(37–3,556)

UA (ng/dL)

6.1 ± 1.3

(2.5–10.7)

FBS (mg/dL)

99.4 ± 19.6

(78–201)

HbA1c (%)

5.7 ± 0.6

(4.9–8.6)

LH (mIU/mL)

3.6 ± 4.2

(0.1–24.8)

FSH (mIU/mL)

8.1 ± 8.9

(0.1–55.4)

Testosterone (ng/mL)

2.2 ± 0.6

(0.3–2.9)

Prolactin (ng/mL)

10.8 ± 12.4

(0.3–82.9)

DHEA-S (μg/dL)

213.5 ± 94.9

(24–490)

IGF-1 (ng/mL)

140.5 ± 44.3

(62–374)

Insulin (μU/mL)

6.5 ± 4.2

(0.6–22.2)

Cortisol (μg/dL)

9.9 ± 3.9

(0.8–21.0)IPSS

8.6 ± 5.8

(0–26)

BDI

16.2 ± 9.4(1–42)

SHIM

9.7 ± 6.6

(1–25)

EHS

2.2 ± 1.2

(1–4)

Total

46.9 ± 12.1

(26–80)Mental subscore12.7 ± 5.1(5–25)

Physical subscore19.1 ± 5.2(7–33)

Sexual subscore15.1 ± 4.4(5–25)AMS

Results
Patients’ characteristics are summarized in Table 1.
The chief complaints of the patients, if we presume tochoose three, although symptoms were usually compli‐
cated and overlapping, were mental function in 35 pa‐
tients (31.8%), physical function in 49 patients (44.6%),
and sexual function in 26 patients (23.6%). Mean patientage was 53.5 years and BMI was 25.1 kg/m2. The mean
concentrations of all laboratory values were within nor‐
mal limits, whereas those of the endocrinologic values
varied widely. The mean serum testosterone was 2.2 ±0.6 ng/mL. From the questionnaires, lower urinary
tract symptoms were moderate as evaluated by the mean
IPSS score of 8.6. Severity of depression was cate‐gorized as mild mood disturbance based on the mean
BDI score of 16.2. Erectile dysfunction was categorized
as moderate based on the mean scores of the SHIM andEHS of 9.7 and 2.2, respectively. The mean AMS
score of 46.9 was considered moderate, and the mental,
physical, and sexual subscores were 12.7, 19.1, and 15.1,
respectively.

AMS, Aging Males Symptoms; BDI, Beck Depression Inventory;
BMI, body mass index; DHEA-S, dehydroepiandrosterone sulfate;
EHS, Erection Hardness Score; FBS, fasting blood sugar; FSH,
follicle-stimulating hormone; HbA1c, hemoglobin A1c; HDL,
high-density lipoprotein; IGF-1, insulin-like growth factor-1; IPSS,
International Prostate Symptom Score; LDL, low-density
lipoprotein; LH, luteinizing hormone; SHIM, Sexual HealthInventory for Men; UA, uric acid.

Findings before and after TRT in the SG and NSG canbe compared in Tables 2 and 3. Among the 110 patients,
77 (effectiveness rate of 70.0%) were classified into
the SG. TRT was effective in 23 patients (65.7%),
35 patients (71.4%), and 19 patients (73.1%), withmental, physical, and sexual dysfunction. In the SG,
serum testosterone increased significantly from 2.2 to
4.6 ng/mL. With respect to LOH-related symptoms, theBDI, SHIM, and AMS scores improved significantly,

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Ishikawa et al.

Table 2

Endocrinological variables and questionnaires before and after TRT
Satisfaction group (N = 77; 70.0%)

Total cholesterol (mg/dL)

p-value

BeforeAfter215.9 ± 57.6

214.9 ± 77.1

0.925

HDL cholesterol (mg/dL)

56.9 ± 15.1

65.5 ± 17.1

0.4

LDL cholesterol (mg/dL)

124.6 ± 36.2

112.3 ± 14.8

0.753

Triglyceride (mg/dL)

224.1 ± 465.0

226.4 ± 486.0

0.202

UA (ng/dL)

5.9 ± 1.3

5.2 ± 1.4

0.463

FBS (mg/dL)

98.5 ± 19.7

101.6 ± 20.5

0.08

HbA1c (%)

5.7 ± 0.6

5.5 ± 0.3

0.236

LH (mIU/mL)

3.8 ± 4.6

3.2 ± 4.0

0.025

FSH (mIU/mL)

8.5 ± 9.7

9.1 ± 13.1

0.028

Testosterone (ng/mL)

2.2 ± 0.7

4.6 ± 3.1

0.001

Prolactin (ng/mL)

10.5 ± 11.7

11.1 ± 4.3

0.043

DHEA-S (μg/dL)

210.3 ± 96.7

132.8 ± 67.5

0.753

IGF-1 (ng/mL)

141.1 ± 37.7

112.8 ± 41.5

0.674

Insulin (μU/mL)

6.6 ± 4.6

18.0 ± 29.1

0.001

Cortisol (μg/dL)

9.7 ± 3.8

9.8 ± 3.9

0.663

IPSS

9.1 ± 6.0

8.4 ± 5.6

0.098

BDI

16.7 ± 9.5

10.7 ± 8.6

0.001

SHIM

9.2 ± 6.4

13.0 ± 7.6

0.002

EHS

2.2 ± 1.3

2.8 ± 0.9

0.041

Total

47.9 ± 11.7

39.6 ± 13.1

0.001

Mental subscore13.1 ± 5.1

11.6 ± 4.6

0.241

Physical subscore

19.5 ± 5.1

16.0 ± 5.6

0.001

Sexual subscore15.2 ± 4.4

11.9 ± 4.1

0.001

AMS

AMS, Aging Males Symptoms; BDI, Beck Depression Inventory; BMI, body mass index; DHEA-S,
dehydroepiandrosterone sulfate; EHS, Erection Hardness Score; FBS, fasting blood sugar; FSH,
follicle-stimulating hormone; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; IGF-1,
insulin-like growth factor-1; IPSS, International Prostate Symptom Score; LDL, low-density
lipoprotein; LH, luteinizing hormone; SHIM, Sexual Health Inventory for Men; TRT, testosterone
replacement treatment; UA, uric acid.

whereas no significant improvement was observed in the
IPSS. In the NSG, serum testosterone also significantly
increased from 2.2 to 3.4 ng/mL. The symptom scores of
the BDI, SHIM, and AMS also improved significantly
similar to those in the SG, and no significant improve‐
ment was observed in the IPSS.
The relationship between patient satisfaction andimprovement of the questionnaire scores after TRT isshown in Fig. 1. No significant differences in the amountof change in the BDI, SHIM, and AMS scores were
found between the SG and NSG. We classified the groupwith improvement of the AMS (by ≥8 points) and thegroup with no improvement of the AMS (by ≤7 points)
according to the amount of change in the AMS anddetermined the ratio of patient satisfaction with TRT ineach patient group. Thirty-nine patients (65.0%) weresatisfied with TRT, even for the group with improvementof the AMS (by ≥8 points). Nevertheless, as many as
38 patients (76.0%) in the group with no improvementof the AMS (by ≤7 points) were satisfied with TRT(Table 4). Therefore, patient satisfaction did not appear
to be associated with improvement of the AMS score.

Discussion
Some reports have shown that TRT improved moodand depression among mental symptoms, [20] increasedbone and mineral density [21] and lean body mass, anddecreased body fat among physical symptoms, [22] andimproved erectile function and libido among sexual
symptoms in patients with low serum testosterone con‐centrations [23]. Although these merits of TRT havebeen well accepted in the field of urology, the true rate ofeffectiveness of TRT still remains unclear because most

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Table 3

Endocrinological variables and questionnaires before and after TRT
Non-satisfaction group (N = 33; 30.0%)

Total cholesterol (mg/dL)

p-value

BeforeAfter

207.1 ± 40.9

201.4 ± 36.9

0.572

HDL cholesterol (mg/dL)

56.5 ± 13.4

52

0.317

LDL cholesterol (mg/dL)

116.4 ± 37.6

147

0.317

Triglyceride (mg/dL)

204.0 ± 172.6

166.2 ± 72.7

0.9

UA (ng/dL)

6.6 ± 1.3

6.6

0.317

FBS (mg/dL)

101.4 ± 19.6

100.1 ± 9.1

0.533

HbA1c (%)

5.8 ± 0.8

6.9

0.317

LH (mIU/mL)

3.0 ± 3.0

2.0 ± 1.7

0.57

FSH (mIU/mL)

7.1 ± 6.8

2.8 ± 1.1

0.655

Testosterone (ng/mL)

2.2 ± 0.5

3.4 ± 1.7

0.006

Prolactin (ng/mL)

11.3 ± 14.2

8.63

0.317

DHEA-S (μg/dL)

221.1 ± 91.5

102

0.317

IGF-1 (ng/mL)

141.1 ± 37.7

90

0.317

Insulin (μU/mL)

6.2 ± 3.2

13.9 ± 11.4

0.001

Cortisol (μg/dL)

10.3 ± 4.1

11.9 ± 3.3

0.65

IPSS

7.5 ± 5.1

5.5 ± 5.6

0.082

BDI

14.8 ± 9.2

8.5 ± 8.6

0.015

SHIM

10.9 ± 7.1

13.3 ± 7.1

0.046

EHS

2.3 ± 1.1

2.6 ± 1.3

0.124

44.5 ± 13.0

34.3 ± 8.9

0.005

AMS
Total
Mental subscore11.8 ± 4.9

8.5 ± 3.2

0.023

Physical subscore18.0 ± 5.5

13.9 ± 3.6

0.032

Sexual subscore

14.7 ± 4.6

12.0 ± 4.8

0.015

AMS, Aging Males Symptoms; BDI, Beck Depression Inventory; BMI, body mass index; DHEA-S,
dehydroepiandrosterone sulfate; EHS, Erection Hardness Score; FBS, fasting blood sugar; FSH,
follicle-stimulating hormone; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; IGF-1,
insulin-like growth factor-1; IPSS, International Prostate Symptom Score; LDL, low-density
lipoprotein; LH, luteinizing hormone; SHIM, Sexual Health Inventory for Men; TRT, testosterone
replacement treatment; UA, uric acid.

studies have been conducted based on the improve‐
ment of symptoms scores of questionnaires such as the
AMS, and physical improvement such as that in bonemineral density, lean body mass, muscle strength, andexercise capacity. Here, we clearly showed that the rateof effectiveness was 70.0% in patients with low serum
testosterone concentration and with symptoms of LOH
treated by TRT. Interestingly, this rate of effectivenesswas very similar to that of the previous study using treat‐ment with herbal medicine (70.9%) [9]. Because neither
the previous study nor ours had placebo arms, the datafrom these studies raised our suspicion that around 70%
of patients might be satisfied when any kind of treatment
intervention was performed. However, we believe that
our finding showing that TRT is effective for 70.0% of
patients with low serum testosterone and at least oneof the symptoms of LOH is valuable in the real-world

clinical setting.
In the present study, we also showed that TRT was
effective in 65.7%, 71.4%, and 73.1% of our patientswith mental, physical, and sexual dysfunction asassessed by patient satisfaction. One report showed that
only three symptoms (decreased frequency of sexual
activity, decreased morning erection, and decreased
libido) were closely associated with testosterone levels
among the symptoms of LOH [24]. This suggests that theincrease of testosterone levels by TRT may be most
expected to cure the sexual symptoms. In addition,
because mental symptoms are surely affected by not only
serum testosterone level but also several environment
factors including social stress in today’s complicatedmodern society, the rate of effectiveness of TRT for men‐tal symptoms was the lowest. We also clearly showedthat the scores of the BDI, SHIM, and AMS improved

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Ishikawa et al.

Fig. 1Comparison of the change of four ratings scores between the satisfaction group (SG) and the non-satisfaction group (NSG). A)
BDI, Beck Depression Inventory; B) SHIM, Sexual Health Inventory for Men; C) EHS, Erection Hardness Score; and D) AMS,
Aging Males Symptoms rating scale.

Table 4

Relationship between change in AMS score and patientsatisfaction after TRT
Patients’ complaints
SatisfiedUnsatisfied

8≤ (N = 60)

39 (65.0%)

21 (35.0%)≥7 (N = 50)

38 (76.0%)

12 (24.0%)

p-value

Change in AMS score
0.21

AMS, Aging Males Symptoms rating scale; TRT, testosterone
replacement treatment.

significantly from before to after TRT regardless ofwhether the patients were in the SG or NSG.
Regarding symptoms of LOH, many studies haveassessed results based on the improvement of the AMS.
Several randomized controlled studies to assess theefficacy of TRT were conducted based on change in the
AMS [25, 26]. The AMS is definitely the most com‐monly used scale worldwide to measure health-related
quality of life and symptoms in aging males. The scale isa self-administered questionnaire whose response cate‐gories for all 17 questions are assigned score points.
At present, the AMS is accepted as a valuable tool
for assessing symptoms of LOH in patients. However,the change in the AMS score as well that in the otherquestionnaires did not differ significantly between the
SG and NSG. Furthermore, we also showed that the rateof patient satisfaction with TRT did not differ between
the groups in terms of successful or failed treatmentsfrom the viewpoint of the change in the AMS score.
These findings are consistent with a previous study withJapanese patients showing that the AMS score worsenedin 28.2% of the patients who were satisfied with TRT
based on the patients’ chief complaints, whereas among
the patients who showed improvement in the AMS score,as many as 69.6% were not fully satisfied with TRT[27]. In the present study as well, 35.0% of the patients
whose AMS score improved by 8 points or more were
not satisfied with TRT, whereas 76.0% of the patients
whose AMS score was improved by 7 points or lesswere satisfied with TRT. The reasons for those who were
not satisfied with TRT are not clear, but we assume thatthey probably had excessive expectations of TRT thatwere not met.
These previous findings and ours suggested thatpatient satisfaction with TRT and changes in the ques‐tionnaire scores do not correlate, and an improvement in
the AMS score does not guarantee symptom relief. We
want to emphasize that it is most important for patientsto be satisfied with their treatment in the real-world
clinical setting because LOH is a quality-of-life diseasein males.
The present study has some limitations. First, we con‐ducted blood tests to determine the biochemical andendocrinological profiles only once. Such testing, espe‐
cially the endocrinological profile, should be repeatedbecause recent studies have shown that testosterone issecreted seasonally and diurnally [28]. Second, we could

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Testosterone replacement treatment

not check life-style factors including smoking, alcohol
drinking, sleeping status, and exercise due to this being a
retrospective study. However, medications were notchanged and/or added during the treatment. Third, the3-month observation period was short and continuing
TRT might change the results. Although these limitations
cannot be ignored, we believe that our findings represent
the current situation in a real-world clinical setting. Fur‐ther long-term observation with a placebo arm will beneeded to resolve these issues.
In conclusion, this is the first study, to our knowledge,
to investigate the rate of effectiveness of TRT in patientswith low serum testosterone concentration and with atleast one symptom of LOH. We clearly showed that TRT

was effective in 70.0% of the patients and that TRT was
effective in 65.7%, 71.4%, and 73.1% of the patientswith mental, physical, and sexual dysfunction. There
were significant improvements in the total scores of the
BDI, SHIM, and AMS both in the SG and the NSG.
However, we also found that patient satisfaction did notcorrelate with the improvement in questionnaire scores,
even with that of the AMS, and that an improvement in
the AMS score does not guarantee symptom relief.

Disclosure
None of the authors have any potential conflicts ofinterest associated with this research.

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